Induction of p21 (CIP1/WAF1/SID1) by estradiol in a breast epithelial cell line transfected with the recombinant estrogen receptor gene:

Thomas, T.; Faaland, Carol A.; Adhikarakunnathu, Sreedevi; Watkins, Linda F.; Thomas, Thresia

doi:10.1023/a:1005925931215

Cited by 17 publications

(22 citation statements)

References 51 publications

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“…Even in the absence of E2, transcript levels of cell cycle inhibitor p21(WAF1) were strongly elevated in ERb1-expressing cells and to a smaller extent also in SK-OV-3 cells expressing the exon-skipped isoforms, suggesting that ERb is able to increase p21(WAF1) levels in a ligand-independent manner. Only in SK-OV-3 cells expressing full-length ERb1, p21(WAF1) transcript levels were further elevated after treatment with E2 alone or in combination with 4-OH TAM, supporting previous studies suggesting an involvement of p21(WAF1) in cellular estrogen response (Planas-Silva & Weinberg 1997, Thomas et al 1998). Given that our results demonstrate that p21(WAF1) mRNA level is increased in Sk-OV-3 cells expressing higher levels of ERb1 and, which exhibit a reduced cell growth, it is tempting to speculate that p21(WAF1) might be a key mediator of the antiproliferative effect of ERb1 in this ovarian cancer model.…”

Section: Discussionsupporting

confidence: 84%

Estrogen receptor β1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

Treeck

Pfeiler

Mitter

et al. 2007

Journal of Endocrinology

100

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Estrogen receptor (ER) b1 and its splice variants are expressed both in ovary and ovarian cancer. We studied the role of ERb1 and two of its splice variants in regulation of gene expression, cellular proliferation, apoptosis, and migration of an ovarian cancer cell line. In this study, we transfected SK-OV-3 ovarian cancer cells with vectors coding for ERb1 or its splice variants ERb-d125 and ERb-d1256, and tested their response to estrogen and tamoxifen in comparison with the untransfected cells. Heterologous expression of ERb1, but not of the exon-deleted ERb variants resulted in notably slower cell growth of SK-OV-3 ovarian cancer cells, an effect accompanied by more than tenfold increase of cyclindependent kinase inhibitor p21(WAF1) transcript levels and a significant reduction of cyclin A2 mRNA levels. SK-OV-3 cells stably overexpressing ERb1 ligand independently also exhibited an increased apoptosis rate and a significantly decreased motility, an effect accompanied by upregulation of fibulin 1c. Our data demonstrate that ERb1, but not the exon-deleted isoforms tested exerts multiple antitumoral effects on SK-OV-3 ovarian cancer cells even in the absence of estradiol or functional ERa.

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Section: Discussionsupporting

confidence: 84%

Estrogen receptor β1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

Treeck

Pfeiler

Mitter

et al. 2007

Journal of Endocrinology

100

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“…The figure shows a representative results of an experiment repeated three times. E 2 -ER in hormone-independent breast cancer cells increases the expression of the Cdk2 inhibitor, p21 (CIP1/WAF1) preventing entry of the cells into S phase of the cell cycle [Wang et al, 1997;Thomas et al, 1998]. …”

Section: Discussionmentioning

confidence: 99%

Characterization of stably transfected fusion protein GFP‐estrogen receptor‐α in MCF‐7 human breast cancer cells

Zhao¹,

Hart²,

Keller³

et al. 2002

J of Cellular Biochemistry

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Tagging hormone receptors with the green fluorescent protein (GFP) has increased our knowledge of ligand dependent sub-cellular trafficking of hormone receptors. However, the effect of the tagged hormone receptor expression on the corresponding wild type hormone receptor and endogenous gene expression has not been investigated. In this study, we constructed a MCF-7 cell line stably expressing GFP-tagged human estrogen receptor-alpha (ER) under control of the tetracycline-on system to determine the effect of GFP-ER expression on cell proliferation and expression of endogenous ER and hormone-responsive genes. Further, the inducible system was applied to determine the ligand dependent turnover rates of GFP-ER protein and mRNA. Our results demonstrate that GFP-ER expression did not affect cell cycling. Independent of ligand, GFP-ER markedly reduced the level of endogenous ER mRNA and protein, suggesting that ER negatively autoregulates its expression. Cisplatin cross-linking studies showed that GFP-ER is associated with nuclear DNA in situ, suggesting that GFP-ER is partially replacing ER at estrogen response elements. Furthermore, GFP-ER expression did not affect the estradiol induced temporal expression of hormone responsive genes c-myc and pS2.

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“…MCF-10A cells have intact cell cycle checkpoint controls (33 -38), are aneuploid but have stable genomes comparable with human mammary epithelial cells (36), and have normal proliferation controls, including contact inhibition (31, 39 -43) and normal apoptotic machinery (37,38,44,45).…”

Section: Methodsmentioning

confidence: 99%

Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells

Morse¹,

Gray

Payne

et al. 2005

Molecular Cancer Therapeutics

245

196

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Apoptosis has long been considered to be the prevailing mechanism of cell death in response to chemotherapy. Currently, a more heterogeneous model of tumor response to therapy is acknowledged wherein multiple modes of death combine to generate the overall tumor response. The resulting mechanisms of cell death are likely determined by the mechanism of action of the drug, the dosing regimen used, and the genetic background of the cells within the tumor. This study describes a nonapoptotic response to docetaxel therapy in human breast cancer cells of increasing cancer progression (MCF-10A, MCF-7, and MDA-mb-231). Docetaxel is a microtubule-stabilizing taxane that is being used in the clinic for the treatment of breast and prostate cancers and small cell carcinoma of the lung. The genetic backgrounds of these cells were characterized for the status of key pathways and gene products involved in drug response and cell death. Cellular responses to docetaxel were assessed by characterizing cell viability, cell cycle checkpoint arrest, and mechanisms of cell death. Mechanisms of cell death were determined by Annexin V binding and scoring of cytology-stained cells by morphology and transmission electron microscopy. The primary mechanism of death was determined to be mitotic catastrophe by scoring of micronucleated cells and cells undergoing aberrant mitosis. Other, nonapoptotic modes of death were also determined. No significant changes in levels of apoptosis were observed in response to docetaxel. [Mol Cancer Ther 2005;4(10):1495 -504]

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Induction of p21 (CIP1/WAF1/SID1) by estradiol in a breast epithelial cell line transfected with the recombinant estrogen receptor gene:

Cited by 17 publications

References 51 publications

Estrogen receptor β1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

Estrogen receptor β1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

Characterization of stably transfected fusion protein GFP‐estrogen receptor‐α in MCF‐7 human breast cancer cells

Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells

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